Determination of somatic mutant frequencies at glycophorin A and T-cell receptor loci for biodosimetry of acute and prolonged irradiation

Саенко, А.С.; Замулаева, И. А.; Smirnova, Svetlana G.; Orlova, Nina; Selivanova, E. I.; Матвеева, Н. П.; Kaplan, Michael A.; Nugis, V.Yu.; Nadezhina, N.M.; Цыб, А Ф

doi:10.1016/s0969-8043(00)00061-0

Cited by 10 publications

(4 citation statements)

References 8 publications

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“…Obviously, stochastic fluctuation and methodological bias of DAPI-banding can largely underlie these results. But the ‘hot’ chromosomal loci is predictably located near the T-cell receptor locus (14q11.2) in our study, which confirms the numerous studies in which the TCR mutant frequency was significantly higher than in control non-irradiated individuals, including of Chernobyl clean-up workers [ 36 , 37 ].…”

Section: Discussionsupporting

confidence: 90%

Pattern of chromosomal aberrations persisting over 30 years in a Chernobyl Nuclear Power Plant accident survivor: study using mFISH

Nikitina¹,

Nugis²,

Astrelina³

et al. 2022

Journal of Radiation Research

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The long-term in vivo cytogenetic effects of high-dose radiation exposure can be traced in accidentally irradiated persons, and particularly useful for developing strategies of monitoring and therapy of such patients, as well as for elucidating the fundamental aspects of hematopoiesis and radiobiology. Using 24-color fluorescent in situ hybridization (mFISH), we analysed the frequency and the spectrum of chromosomal aberrations (CA) in peripheral blood lymphocytes of the Chernobyl Nuclear Power Plant (NPP) accident victim 30, 31, 32 and 33 years after acute accidental exposure to high-dose gamma radiation of the whole body. Totally, 993 metaphase cells were analyzed (or 219, 272, 258, 244 cells each year), of which 297 were aberrant. Our study demonstrated a constant aberrant cell frequency at 28% in 2016–2018 years, while in 2019, a significant increase up to 35% occurred due to contribution of significantly elevated frequency of simple aberrations in the absence of evident recent genotoxic factors. Four clonal aberrations were detected, three of which persisted for more than one year at a frequency up to 2.5% of analyzed cells. The distribution of 731 breakpoints per individual chromosomes was nearly proportional to their physical length, excepting Chromosomes 13 and 20, which were significantly breakpoint-deficient compared to the genome median rate. Monitoring of the long-term effects on chromosomal instability caused by radiation exposure is important for understanding and predicting the long-term effects of ionizing radiation.

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Section: Discussionsupporting

confidence: 90%

Pattern of chromosomal aberrations persisting over 30 years in a Chernobyl Nuclear Power Plant accident survivor: study using mFISH

Nikitina¹,

Nugis²,

Astrelina³

et al. 2022

Journal of Radiation Research

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“…The in vivo TCR mutant assays using T-lymphocytes from human (Kyoizumi et al, 1990;Sawada et al, 1998aSawada et al, , 1998b) and mice Umeki et al, 1997) have been established, and the assays have successfully been used to detect radiationinduced mutations in the patients receiving radiotherapy (Iwamoto et al, 1994;Ishioka et al, 1997) and in the population exposed to radiation during the 1986 Chernobyl accident (Saenko et al, 1998(Saenko et al, , 2000. For the in vitro TCR mutant assay, using cultured human Tlymphocytes, we previously reported that X-raysinduced TCR MF at D 37 (giving 37% survival) was 31.7 × 10 −4 and the relationship appears linear between the mutation induction and the doses .…”

Section: Discussionmentioning

confidence: 99%

“…Although there was no significant doserelated effect observed in atomic bomb survivors, cancer patients who had received radiotherapy (Kyoizumi et al, 1992;Iwamoto et al, 1994;Ishioka et al, 1997) or chemotherapy (Hirota et al, 1994;Sawada et al, 1998a) showed a dose-related increase of TCR mutant frequency (MF). Thus, this assay has been applied to human lymphocytes from people who were directly or indirectly exposed to radiation during and after the Chernobyl accident in Ukraine (Akleyev et al, 1995;Saenko et al, 1998Saenko et al, , 2000Zamulaeva et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Measurement of Mutant Frequency in T-Cell Receptor (Tcr) Gene by Flow Cytometry After X-Irradiation on El-4 Mice Lymphoma Cells

et al. 2007

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-It is well known that somatic mutations are induced by ionizing irradiation. We have previously reported the measurement of mutant frequency (MF) on the T-cell receptor (TCR) gene in mouse T-lymphocytes after irradiation by flow cytomery. In this study, we developed an in vitro system using murine EL-4 lymphoma cells and observed frequency of cells defective in TCR gene expression after exposure to ionizing irradiation. EL-4 cells were stained with fluorescein-labeled anti-CD4 and phycoerythrin-labeled anti-CD3 antibodies. They were analyzed with a flow cytometer to detect mutant EL-4 cells lacking surface expression of TCR/CD3 complexes which showed CD3− , CD4 + due to a somatic mutation at the TCR genes. Mutant cells could be observed at 2 days after 3 Gy irradiation. MF of EL-4 cells was 6.7 × 10 −4 for 0 Gy and the value increased to the maximum level of 39 × 10 −4 between 4 and 8 days after 3 Gy irradiation and these data were found to be best fitted by a linear-quadratic doseresponse model. After the peak value the TCR MF gradually decreased with a half-life of approximately 3.2 days. We also examined the hprt mutant frequencies at seven days after irradiation and the cytokinesisblocked micronucleus frequency at 20 hrs after irradiation. The frequencies of hprt mutation and micronuclei were found to be best fitted by a linear-quadratic dose-response model and a linear dose-response model, respectively. The method to detect mutation on TCR gene is quick and easy in comparison with other methods and is considered useful for the mutagenicity test.

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“…The appearance and persistence of TCR-mutant T cells was detected mostly in the memory CD4+ T cell compartment in a dose-dependent manner in individuals aged 20 or older at the time of bombing ( Kusunoki et al, 2003 ). A relatively robust dose-dependent readout for TCR mutant frequency was suggested after studies on Chernobyl clean-up workers, even at doses of 0.25 Gy ( Saenko et al, 2000 ). This would suggest the use of TCR mutation as a potential biodosimeter relevant to T cell function.…”

Section: Human Biomonitoring and Epidemiological Data On Low Dose Radiation-induced Immunological Changesmentioning

confidence: 99%

Low dose ionizing radiation effects on the immune system

Lumniczky

Impens

Armengol

et al. 2021

Environment International

108

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Ionizing radiation interacts with the immune system in many ways with a multiplicity that mirrors the complexity of the immune system itself: namely the need to maintain a delicate balance between different compartments, cells and soluble factors that work collectively to protect, maintain, and restore tissue function in the face of severe challenges including radiation damage. The cytotoxic effects of high dose radiation are less relevant after low dose exposure, where subtle quantitative and functional effects predominate that may go unnoticed until late after exposure or after a second challenge reveals or exacerbates the effects. For example, low doses may permanently alter immune fitness and therefore accelerate immune senescence and pave the way for a wide spectrum of possible pathophysiological events, including early-onset of age-related degenerative disorders and cancer. By contrast, the so called low dose radiation therapy displays beneficial, anti-inflammatory and pain relieving properties in chronic inflammatory and degenerative diseases. In this review, epidemiological, clinical and experimental data regarding the effects of low-dose radiation on the homeostasis and functional integrity of immune cells will be discussed, as will be the role of immune-mediated mechanisms in the systemic manifestation of localized exposures such as inflammatory reactions. The central conclusion is that ionizing radiation fundamentally and durably reshapes the immune system. Further, the importance of discovery of immunological pathways for modifying radiation resilience amongst other research directions in this field is implied.

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Determination of somatic mutant frequencies at glycophorin A and T-cell receptor loci for biodosimetry of acute and prolonged irradiation

Cited by 10 publications

References 8 publications

Pattern of chromosomal aberrations persisting over 30 years in a Chernobyl Nuclear Power Plant accident survivor: study using mFISH

Pattern of chromosomal aberrations persisting over 30 years in a Chernobyl Nuclear Power Plant accident survivor: study using mFISH

Measurement of Mutant Frequency in T-Cell Receptor (Tcr) Gene by Flow Cytometry After X-Irradiation on El-4 Mice Lymphoma Cells

Low dose ionizing radiation effects on the immune system

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